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To survive, animals must convert sensory information into appropriate behaviours1,2. Vision is a common sense for locating ethologically relevant stimuli and guiding motor responses3-5. How circuitry converts object location in retinal coordinates to movement direction in body coordinates remains largely unknown. Here we show through behaviour, physiology, anatomy and connectomics in Drosophila that visuomotor transformation occurs by conversion of topographic maps formed by the dendrites of feature-detecting visual projection neurons (VPNs)6,7 into synaptic weight gradients of VPN outputs onto central brain neurons. We demonstrate how this gradient motif transforms the anteroposterior location of a visual looming stimulus into the fly's directional escape. Specifically, we discover that two neurons postsynaptic to a looming-responsive VPN type promote opposite takeoff directions. Opposite synaptic weight gradients onto these neurons from looming VPNs in different visual field regions convert localized looming threats into correctly oriented escapes. For a second looming-responsive VPN type, we demonstrate graded responses along the dorsoventral axis. We show that this synaptic gradient motif generalizes across all 20 primary VPN cell types and most often arises without VPN axon topography. Synaptic gradients may thus be a general mechanism for conveying spatial features of sensory information into directed motor outputs.

Naturalistic escape requires versatile context-specific flight with rapid evaluation of local geometry to identify and use efficient escape routes. It is unknown how spatial navigation and escape circuits are recruited to produce context-specific flight. Using mice, we show that activity in cholecystokinin-expressing hypothalamic dorsal premammillary nucleus (PMd-cck) cells is sufficient and necessary for context-specific escape that adapts to each environment's layout. In contrast, numerous other nuclei implicated in flight only induced stereotyped panic-related escape. We reasoned the dorsal premammillary nucleus (PMd) can induce context-specific escape because it projects to escape and spatial navigation nuclei. Indeed, activity in PMd-cck projections to thalamic spatial navigation circuits is necessary for context-specific escape induced by moderate threats but not panic-related stereotyped escape caused by perceived asphyxiation. Conversely, the PMd projection to the escape-inducing dorsal periaqueductal gray projection is necessary for all tested escapes. Thus, PMd-cck cells control versatile flight, engaging spatial navigation and escape circuits.

To evade their predators, animals must quickly detect potential threats, gauge risk, and mount a response. Putative neural circuits responsible for these tasks have been isolated in laboratory studies. However, it is unclear whether and how these circuits combine to generate the flexible, dynamic sequences of evasion behavior exhibited by wild, freely moving animals. Here, we report that evasion behavior of wild fish on a coral reef is generated through a sequence of well-defined decision rules that convert visual sensory input into behavioral actions. Using an automated system to present visual threat stimuli to fish in situ, we show that individuals initiate escape maneuvers in response to the perceived size and expansion rate of an oncoming threat using a decision rule that matches dynamics of known loom-sensitive neural circuits. After initiating an evasion maneuver, fish adjust their trajectories using a control rule based on visual feedback to steer away from the threat and toward shelter. These decision rules accurately describe evasion behavior of fish from phylogenetically distant families, illustrating the conserved nature of escape decision-making. Our results reveal how the flexible behavioral responses required for survival can emerge from relatively simple, conserved decision-making mechanisms.

While foraging, animals can form inter- and intraspecific social signalling networks to avoid similar predators. We report here that foragers of different native Asian honey bee species can detect and use a specialized alarm pheromone component, benzyl acetate (BA), to avoid danger. We analysed the volatile alarm pheromone produced by attacked workers of the most abundant native Asian honey bee, Apis cerana and tested the responses of other bee species to these alarm signals. As compared to nest guards, A. cerana foragers produced 3.38 fold higher levels of BA. In foragers, BA and (E)-dec-2-en-1-yl acetate (DA) generated the strongest antennal electrophysiological responses. BA was also the only compound that alerted flying foragers and inhibited A. cerana foraging. BA thereby decreased A. cerana foraging for risky sites. Interestingly, although BA occurs only in trace amounts and is nearly absent in sympatric honeybee species (respectively only 0.07% and 0.44% as much in A. dorsata and A. florea), these floral generalists detected and avoided BA as strongly as they did to their own alarm pheromone on natural inflorescences. These results demonstrate that competing pollinators can take advantage of alarm signal information provided by other species.

Predation is a fundamental interaction between species, yet it is unclear what escape strategies are effective for prey survival. Classical theory proposes that prey should either escape in a direction that conforms to a performance optimum or that is random and therefore unpredictable. Here, we show that larval zebrafish (Danio rerio) instead use a mixed strategy that may be either random or directed. This was determined by testing classic theory with measurements of the escape direction in response to a predator robot. We found that prey consistently escaped in a direction contralateral to the robot when approached from the side of the prey's body. At such an orientation, the predator appeared in the prey's central visual field and the contralateral response was consistent with a model of strategy that maximizes the distance from the predator. By contrast, when the robot approached the rostral or caudal ends of the body, and appeared in the prey's peripheral vision, the escape showed an equal probability of a contralateral or ipsilateral direction. At this orientation, a contralateral response offered little strategic advantage. Therefore, zebrafish larvae adopt an escape strategy that maximizes distance from the threat when strategically beneficial and that is otherwise random. This sensory-mediated mixed strategy may be employed by a diversity of animals and offers a new paradigm for understanding the factors that govern prey survival.

The remarkable adhesive capabilities of geckos have garnered attention from scientists and the public for centuries. Geckos are known to have an adhesive load-bearing capacity far in excess (by 100-fold or more) of that required to support their body mass or accommodate the loading imparted during maximal locomotor acceleration. Few studies, however, have investigated the ecological contexts in which geckos use their adhesive system and how this may influence its properties. Here we develop a modelling framework to assess whether their prodigious adhesive capacity ever comes under selective challenge. Our investigation is based upon observations of escape-induced aerial descents of canopy-dwelling arboreal geckos that are rapidly arrested by clinging to leaf surfaces in mid-fall. We integrate ecological observations, adhesive force measurements, and body size and shape measurements of museum specimens to conduct simulations. Using predicted bending mechanics of petioles and leaf midribs, we find that the drag coefficient of the gecko, the size of the gecko and the size of the leaf determine impact forces. Regardless of the landing surface, safety factors for geckos range from a maximum of just over 10 to a minimum of well under one, which would be the point at which the adhesive system fails. In contrast to previous research that intimates that gecko frictional adhesive capacity is excessive relative to body mass, we demonstrate that realistic conditions in nature may result in frictional capacity being pushed to its limit. The rapid arrest of the lizard from its falling velocity likely results in the maximal loading to which the adhesive system is exposed during normal activities. We suggest that such activities might be primary determinants in driving their high frictional adhesive capacity.

An escape response is a rapid manoeuvre used by prey to evade predators. Performing this manoeuvre at greater speed, in a favourable direction, or from a longer distance have been hypothesized to enhance the survival of prey, but these ideas are difficult to test experimentally. We examined how prey survival depends on escape kinematics through a novel combination of experimentation and mathematical modelling. This approach focused on zebrafish (Danio rerio) larvae under predation by adults and juveniles of the same species. High-speed three-dimensional kinematics were used to track the body position of prey and predator and to determine the probability of behavioural actions by both fish. These measurements provided the basis for an agent-based probabilistic model that simulated the trajectories of the animals. Predictions of survivorship by this model were found by Monte Carlo simulations to agree with our observations and we examined how these predictions varied by changing individual model parameters. Contrary to expectation, we found that survival may not be improved by increasing the speed or altering the direction of the escape. Rather, zebrafish larvae operate with sufficiently high locomotor performance due to the relatively slow approach and limited range of suction feeding by fish predators. We did find that survival was enhanced when prey responded from a greater distance. This is an ability that depends on the capacity of the visual and lateral line systems to detect a looming threat. Therefore, performance in sensing, and not locomotion, is decisive for improving the survival of larval fish prey. These results offer a framework for understanding the evolution of predator-prey strategy that may inform prey survival in a broad diversity of animals.

Deimatic or 'startle' displays cause a receiver to recoil reflexively in response to a sudden change in sensory input. Deimatism is sometimes implicitly treated as a form of aposematism (unprofitability associated with a signal). However, the fundamental difference is, in order to provide protection, deimatism does not require a predator to have any learned or innate aversion. Instead, deimatism can confer a survival advantage by exploiting existing neural mechanisms in a way that releases a reflexive response in the predator. We discuss the differences among deimatism, aposematism, and forms of mimicry, and their ecological and evolutionary implications. We highlight outstanding questions critical to progress in understanding deimatism.

Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically

Escape behavior is a common antipredator strategy among wild animals. Here, we investigated the effect of four factors on the vigilance behavior of the endemic Cyprus rock agama (Laudakia cypriaca). Flight initiation distance (FID, the minimum distance to which an observer can approach a lizard before it flees) was measured in relation to the type of location (tourist vs. nontourist area), the observer's starting distance, air temperature, and substrate temperature. We collected data for 39 agamas in tourist areas and 34 of these lizards in nontourist areas. As a whole, the mean starting distance was 10.5 m and the FID was 3.6 m. The average substrate temperature was 34.0°C and the average air temperature 29.6°C. Only the type of area affected the agamas' escape decisions with FID being 1.8 m shorter in tourist areas than in nontourist areas (2.7 m vs. 4.5 m). This is probably due to the habituation of lizards to the presence of humans in the former areas. This study shows that tourism strongly affects the behavior of lizards, which may have consequences for the functioning of the population. Tourists can increase the safety of lizards by creating a human shield to deter predators. Once the tourist season is over, lizards may become more vulnerable to predators., (© 2023 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

After detecting an approaching predator, animals make a decision when to flee. Prey will initiate flight soon after detecting a predator so as to minimize attentional costs related to on-going monitoring of the whereabouts of the predator. Such costs may compete with foraging and other maintenance activities and hence be larger than the costs of immediate flight. The drivers of interspecific variation in escape strategy are poorly known. Here we investigated the morphological, life history and natural history traits that correlate with variation in avian escape strategy across a sample of 96 species of birds. Brain mass, body size, habitat structure and group size were the main predictors of escape strategy. The direction of the effect of these traits was consistent with selection for a reduction of monitoring costs. Therefore, attentional costs depend on relative brain size, which determines the ability to monitor the whereabouts of potential predators and the difficulty of this task as reflected by habitat and social complexity. Thus brain size, and the cognitive functions associated with it, constitute a general framework for explaining the effects of body size, habitat structure and sociality identified as determinants of avian escape strategy.

Since 1986, studies about the escape decisions made by prey are grounded in optimal escape theory (OET) which states that prey will initiate escape when the risk of remaining and the costs of leaving are equal. However, a recent hypothesis, Flush Early and Avoid the Rush (FEAR), acknowledged that the cost of monitoring approaching predators might be a ubiquitous cost. The FEAR hypothesis predicts that prey will generally flee soon after they detect a predator so as to minimize the costs incurred by monitoring the predator. Knowing whether animals flee to reduce monitoring costs is of applied interest because wildlife managers use escape behavior to create set-back zones to reduce human-wildlife conflict. Here we provide the most comprehensive assessment of the FEAR hypothesis using data collected from 178 bird species representing 67 families from two continents. The FEAR hypothesis explains escape behavior in 79% of studied species. Because the FEAR hypothesis is a widespread phenomenon that drives escape behavior in birds, alert distance must be systematically incorporated into the design of set-back zones to protect vulnerable species.

Visual signaling in animals can serve many uses, including predator deterrence and mate attraction. In many cases, signals used to advertise unprofitability to predators are also used for intraspecific communication. Although aposematism and mate choice are significant forces driving the evolution of many animal phenotypes, the interplay between relevant visual signals remains little explored. Here, we address this question in the aposematic passion-vine butterfly Heliconius erato by using color- and pattern-manipulated models to test the contributions of different visual features to both mate choice and warning coloration. We found that the relative effectiveness of a model at escaping predation was correlated with its effectiveness at inducing mating behavior, and in both cases wing color was more predictive of presumptive fitness benefits than wing pattern. Overall, however, a combination of the natural (local) color and pattern was most successful for both predator deterrence and mate attraction. By exploring the relative contributions of color versus pattern composition in predation and mate preference studies, we have shown how both natural and sexual selection may work in parallel to drive the evolution of specific animal color patterns.

Remarkable advances have been made in recent years in our understanding of innate behavior and the underlying neural circuits. In particular, a wealth of neuromodulatory mechanisms have been uncovered that can alter the input-output relationship of a hereditary neural circuit. It is now clear that this inbuilt flexibility allows animals to modify their behavioral responses according to environmental cues, metabolic demands and physiological states. Here, we discuss recent insights into how modulation of neural circuits impacts innate behavior, with a special focus on how environmental cues and internal physiological states shape different aspects of feeding behavior in Drosophila.

Older adults often report less affective reactivity to interpersonal tensions than younger individuals, but few studies have directly investigated mechanisms explaining this effect. The current study examined whether older adults' differential endorsement of goals, appraisals, and emotion regulation strategies (i.e., conflict avoidance/de-escalation, self-distraction) during a controlled negative social interaction may explain age differences in affective and cardiovascular responses to the conflict discussion. Participants (N = 159; 80 younger adults, 79 older adults) discussed hypothetical dilemmas with disagreeable confederates. Throughout the laboratory session, participants' subjective emotional experience, blood pressure, and pulse rate were assessed. Older adults generally exhibited less reactivity (negative affect reactivity, diastolic blood pressure reactivity, and pulse rate reactivity) to the task and more pronounced positive and negative affect recovery following the task than did younger adults. Older adults appraised the task as more enjoyable and the confederate as more likeable and more strongly endorsed goals to perform well on the task, which mediated age differences in negative affect reactivity, pulse rate reactivity, and positive affect recovery (i.e., increases in posttask positive affect), respectively. In addition, younger adults showed increased negative affect reactivity with greater use of self-distraction, whereas older adults did not. Together, findings suggest that older adults respond less negatively to unpleasant social interactions than younger adults, and these responses are explained in part by older adults' pursuit of different motivational goals, less threatening appraisals of the social interaction, and more effective use of self-distraction, compared with younger adults.

Escaping a predator is one of the keys to success for any living creature. The performance of adults (males, females, and ovigerous females) of the cyclopoid copepod Oithona davisae exposed to an electrical stimulus is analysed as a function of temperature by measuring characteristic parameters associated with the escape movement (distance covered, duration of the appendage movement, mean and maximum escape speeds, Reynolds number). In addition, as a proxy for the efficiency of the motion, the Strouhal number was calculated. The escape performance showed temperature-dependent relationships within each adult state, as well as differences between sexes; additionally, changes owing to the presence of the egg sac were recorded in females. In a broader perspective, the results collected reveal the occurrence of different behavioural adaptations in males and females, adding to the comprehension of the mechanisms by which O. davisae interacts with its environment and shedding new light on the in situ population dynamics of this species., (© 2024. The Author(s).)

Optimal escape theory states that animals should counterbalance the costs and benefits of flight when escaping from a potential predator. However, in apparent contradiction with this well-established optimality model, birds and mammals generally initiate escape soon after beginning to monitor an approaching threat, a phenomena codified as the "Flush Early and Avoid the Rush" (FEAR) hypothesis. Typically, the FEAR hypothesis is tested using correlational statistics and is supported when there is a strong relationship between the distance at which an individual first responds behaviorally to an approaching predator (alert distance, AD), and its flight initiation distance (the distance at which it flees the approaching predator, FID). However, such correlational statistics are both inadequate to analyze relationships constrained by an envelope (such as that in the AD-FID relationship) and are sensitive to outliers with high leverage, which can lead one to erroneous conclusions. To overcome these statistical concerns we develop the phi index (Φ), a distribution-free metric to evaluate the goodness of fit of a 1:1 relationship in a constraint envelope (the prediction of the FEAR hypothesis). Using both simulation and empirical data, we conclude that Φ is superior to traditional correlational analyses because it explicitly tests the FEAR prediction, is robust to outliers, and it controls for the disproportionate influence of observations from large predictor values (caused by the constrained envelope in AD-FID relationship). Importantly, by analyzing the empirical data we corroborate the strong effect that alertness has on flight as stated by the FEAR hypothesis.

Concern is growing over the effects of neonicotinoid pesticides, which can impair honey bee cognition. We provide the first demonstration that sublethal concentrations of imidacloprid can harm honey bee decision-making about danger by significantly increasing the probability of a bee visiting a dangerous food source. Apis cerana is a native bee that is an important pollinator of agricultural crops and native plants in Asia. When foraging on nectar containing 40 µg/L (34 ppb) imidacloprid, honey bees (Apis cerana) showed no aversion to a feeder with a hornet predator, and 1.8 fold more bees chose the dangerous feeder as compared to control bees. Control bees exhibited significant predator avoidance. We also give the first evidence that foraging by A. cerana workers can be inhibited by sublethal concentrations of the pesticide, imidacloprid, which is widely used in Asia. Compared to bees collecting uncontaminated nectar, 23% fewer foragers returned to collect the nectar with 40 µg/L imidacloprid. Bees that did return respectively collected 46% and 63% less nectar containing 20 µg/L and 40 µg/L imidacloprid. These results suggest that the effects of neonicotinoids on honey bee decision-making and other advanced cognitive functions should be explored. Moreover, research should extend beyond the classic model, the European honey bee (A. mellifera), to other important bee species.

Animal development is coupled with innate behaviors that maximize chances of survival. Here, we show that the prothoracicotropic hormone (PTTH), a neuropeptide that controls the developmental transition from juvenile stage to sexual maturation, also regulates light avoidance in Drosophila melanogaster larvae. PTTH, through its receptor Torso, acts on two light sensors--the Bolwig's organ and the peripheral class IV dendritic arborization neurons--to regulate light avoidance. We found that PTTH concomitantly promotes steroidogenesis and light avoidance at the end of larval stage, driving animals toward a darker environment to initiate the immobile maturation phase. Thus, PTTH controls the decisions of when and where animals undergo metamorphosis, optimizing conditions for adult development.

Mutations in valosin-containing protein (VCP) cause a rare, autosomal dominant disease called inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD). One-third of patients with IBMPFD develop frontotemporal dementia, characterized by an extensive neurodegeneration in the frontal and temporal lobes. Neuropathologic hallmarks include nuclear and cytosolic inclusions positive to ubiquitin and transactive response DNA-binding protein 43 (TDP-43) in neurons and glial activation in affected regions. However, the pathogenic mechanisms by which mutant VCP triggers neurodegeneration remain unknown. Herein, we generated a mouse model selectively overexpressing a human mutant VCP in neurons to study pathogenic mechanisms of mutant VCP-mediated neurodegeneration and cognitive impairment. The overexpression of VCPA232E mutation in forebrain regions produced significant progressive impairments of cognitive function, including deficits in spatial memory, object recognition, and fear conditioning. Although overexpressed or endogenous VCP did not seem to focally aggregate inside neurons, TDP-43 and ubiquitin accumulated with age in transgenic mouse brains. TDP-43 was also found to co-localize with stress granules in the cytosolic compartment. Together with the appearance of high-molecular-weight TDP-43 in cytosolic fractions, these findings demonstrate the mislocalization and accumulation of abnormal TDP-43 in the cytosol of transgenic mice, which likely lead to an increase in cellular stress and cognitive impairment. Taken together, these results highlight an important pathologic link between VCP and cognition.

This study aimed to evaluate and validate the Portuguese version of the Fear of COVID-19 Scale (FCV-19S) and also to investigate the association of sociodemographic variables with the FCV-19S scores recorded in a sample of 3,495 women and 1,143 men recruited through a cross-sectional online survey in the population of the State of Parana, Southern Brazil. The statistical analysis indicated that the Portuguese version of the FCV-19S has a unidimensional structure with robust psychometric properties. Besides, the mean score comparison and multiple logistic regression revealed statistically significant differences in gender, age groups, and educational status. These findings can provide a better understanding of the most emotionally vulnerable people in Brazil and assist in planning mental health actions. [ABSTRACT FROM AUTHOR]

Vulnerabilities to fear‐related disorders can be enhanced following early life adversity. This study sought to determine whether post‐weaning social isolation (PSI), an animal model of early life adversity, alters the development of social fear in an innovative model of conditioned social fear. Male and female Sprague‐Dawley rats underwent either social rearing (SR) or PSI for 4 weeks following weaning. Rats were then assigned to groups consisting of either Footshock only, Social conditioned stimulus (CS) only, or Paired footshock with a social CS. Social behavior was assessed the next day. We observed a novel behavioral response in PSI rats, running in circles, that was rarely observed in SR rats; moreover, this behavior was augmented after Paired treatment in PSI rats. Other social behaviors were altered by both PSI and Paired footshock and social CS. The mammalian target of rapamycin (mTOR) pathway was assessed using immunohistochemistry for phosphorylated ribosomal protein S6 (pS6) in subregions of the prefrontal cortex (PFC) and amygdala. Paired treatment produced opposite effects in the PFC and amygdala in males, but no differences were observed in females. Conditioned social fear produced alterations in social behavior and the mTOR pathway that are dependent upon rearing condition and sex. [ABSTRACT FROM AUTHOR]

In the current commentary, we discuss Stoltenberg and colleagues finding (reported in this issue) that variation in the serotonin transporter gene (5-HTTLPR) is associated with prosocial behavior via effects on anxiety in social situations. We note how their results are consistent with evidence from the psychopharmacological literature and illustrate how a mediational framework can inform understanding of genetic and psychological associations, and we suggest that future studies that manipulate social context could further elucidate the relationship between genes involved in serotonin regulation and prosocial behavior.

BackgroundResponding to noxious stimuli by invoking an appropriate escape response is critical for survival of an organism. The sensations of small and large changes in temperature in most organisms have been studied separately in the context of thermotaxis and nociception, respectively. Here we use the nematode C. elegans to address the neurogenetic basis of responses to thermal stimuli over a broad range of intensities.ResultsC. elegans responds to aversive temperature by eliciting a stereotypical behavioral sequence. Upon sensation of the noxious stimulus, it moves backwards, turns and resumes forward movement in a new direction. In order to study the response of C. elegans to a broad range of noxious thermal stimuli, we developed a novel assay that allows simultaneous characterization of multiple aspects of escape behavior elicited by thermal pulses of increasing amplitudes. We exposed the laboratory strain N2, as well as 47 strains with defects in various aspects of nervous system function, to thermal pulses ranging from ΔT = 0.4°C to 9.1°C and recorded the resulting behavioral profiles.ConclusionsThrough analysis of the multidimensional behavioral profiles, we found that the combinations of molecules shaping avoidance responses to a given thermal pulse are unique. At different intensities of aversive thermal stimuli, these distinct combinations of molecules converge onto qualitatively similar stereotyped behavioral sequences.

Escaping from predators often demands that animals rapidly negotiate complex environments. The smallest animals attain relatively fast speeds with high frequency leg cycling, wing flapping or body undulations, but absolute speeds are slow compared to larger animals. Instead, small animals benefit from the advantages of enhanced maneuverability in part due to scaling. Here, we report a novel behavior in small, legged runners that may facilitate their escape by disappearance from predators. We video recorded cockroaches and geckos rapidly running up an incline toward a ledge, digitized their motion and created a simple model to generalize the behavior. Both species ran rapidly at 12-15 body lengths-per-second toward the ledge without braking, dove off the ledge, attached their feet by claws like a grappling hook, and used a pendulum-like motion that can exceed one meter-per-second to swing around to an inverted position under the ledge, out of sight. We discovered geckos in Southeast Asia can execute this escape behavior in the field. Quantification of these acrobatic behaviors provides biological inspiration toward the design of small, highly mobile search-and-rescue robots that can assist us during natural and human-made disasters. We report the first steps toward this new capability in a small, hexapedal robot.

Functional recovery from cutaneous injury requires not only the healing and regeneration of skin cells but also reinnervation of the skin by somatosensory peripheral axon endings. To investigate how sensory axon regeneration and wound healing are coordinated, we amputated the caudal fins of zebrafish larvae and imaged somatosensory axon behavior. Fin amputation strongly promoted the regeneration of nearby sensory axons, an effect that could be mimicked by ablating a few keratinocytes anywhere in the body. Since injury produces the reactive oxygen species hydrogen peroxide (H(2)O(2)) near wounds, we tested whether H(2)O(2) influences cutaneous axon regeneration. Exposure of zebrafish larvae to sublethal levels of exogenous H(2)O(2) promoted growth of severed axons in the absence of keratinocyte injury, and inhibiting H(2)O(2) production blocked the axon growth-promoting effects of fin amputation and keratinocyte ablation. Thus, H(2)O(2) signaling helps coordinate wound healing with peripheral sensory axon reinnervation of the skin.

Peripheral cannabinoid receptors exert a powerful inhibitory control over pain initiation, but the endocannabinoid signal that normally engages this intrinsic analgesic mechanism is unknown. To address this question, we developed a peripherally restricted inhibitor (URB937) of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of the endocannabinoid anandamide. URB937 suppressed FAAH activity and increased anandamide levels outside the rodent CNS. Despite its inability to access brain and spinal cord, URB937 attenuated behavioral responses indicative of persistent pain in rodent models of peripheral nerve injury and inflammation and prevented noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CB₁ cannabinoid receptor blockade prevented these effects. These results suggest that anandamide-mediated signaling at peripheral CB₁ receptors controls the access of pain-related inputs to the CNS. Brain-impenetrant FAAH inhibitors, which strengthen this gating mechanism, might offer a new approach to pain therapy.

Migratory songbirds have the remarkable ability to extract directional information from the Earth's magnetic field 1,2 . The exact mechanism of this light-dependent magnetic compass sense, however, is not fully understood. The most promising hypothesis focuses on the quantum spin dynamics of transient radical pairs formed in cryptochrome proteins in the retina 3-5 . Frustratingly, much of the supporting evidence for this theory is circumstantial, largely because of the extreme challenges posed by genetic modification of wild birds. Drosophila has therefore been recruited as a model organism, and several influential reports of cryptochrome-mediated magnetic field effects on fly behaviour have been widely interpreted as support for a radical pair-based mechanism in birds 6-23 . Here we report the results of an extensive study testing magnetic field effects on 97,658 flies moving in a two-arm maze and on 10,960 flies performing the spontaneous escape behaviour known as negative geotaxis. Under meticulously controlled conditions and with vast sample sizes, we have been unable to find evidence for magnetically sensitive behaviour in Drosophila. Moreover, after reassessment of the statistical approaches and sample sizes used in the studies that we tried to replicate, we suggest that many-if not all-of the original results were false positives. Our findings therefore cast considerable doubt on the existence of magnetic sensing in Drosophila and thus strongly suggest that night-migratory songbirds remain the organism of choice for elucidating the mechanism of light-dependent magnetoreception., (© 2023. The Author(s).)

We designed a behavioral task called One-Trial Trace Escape Reaction (OTTER), in which rats incidentally associate two temporally discontinuous stimuli: a neutral acoustic cue (CS) with an aversive stimulus (US) which occurs two seconds later (CS-2s-US sequence). Rats are first habituated to two similar environmental contexts (A and B), each consisting of an interconnected dark and light chamber. Next, rats experience the CS-2s-US sequence in the dark chamber of one of the contexts (either A or B); the US is terminated immediately after a rat escapes into the light chamber. The CS-2s-US sequence is presented only once to ensure the incidental acquisition of the association. The recall is tested 24 h later when rats are presented with only the CS in the alternate context (B or A), and their behavioral response is observed. Our results show that 59% of the rats responded to the CS by escaping to the light chamber, although they experienced only one CS-2s-US pairing. The OTTER task offers a flexible high throughput tool to study memory acquired incidentally after a single experience. Incidental one-trial acquisition of association between temporally discontinuous events may be one of the essential components of episodic memory formation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Radostova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)